Trial of Ulixertinib in Combination With Hydroxychloroquine in Patients With Advanced Gastrointestinal (GI) Malignancies

This is an open-label, multicenter, phase II basket study of ulixertinib in combination with hydroxychloroquine in patients with advanced gastrointestinal malignancies harboring rat sarcoma virus (RAS), a member of the rapidly accelerated fibrosarcoma (non-V600 BRAF), extracellular signal-regulated kinase (ERK), or mitogen-activated protein kinase (MEK) mutations. The trial will have five baskets based on disease primary as listed below. Basket 1: Cholangiocarcinoma including intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, or extrahepatic cholangiocarcinoma; Basket 2: Pancreatic adenocarcinoma; Basket 3: Colorectal adenocarcinoma; Basket 4: Esophageal adenocarcinoma, esophageal squamous cell carcinoma, or gastroesophageal junction (GEJ) adenocarcinoma; Basket 5: Gastric adenocarcinoma. While the overall trial is a basket design, each basket will operate as a Simon two-stage design and therefore, will open to enrollment in two-stages. Total enrollment for Stage 1 is targeted at approximately 65 patients with 13 patients per group. Additional patients may be enrolled as appropriate. Total enrollment for Stage 2 is targeted to approximately 150 patients with up to 30 patients per group. Additional patients may be enrolled as appropriate.